Although it is clear that the central nervous system (CNS) exerts considerable influence over metabloic events, not until recently has an emphasis been placed upon these interactions by researchers. The proposed research will focus upon several clinically important issues regarding this interaction. The amount of adiposity or body-weight of animals is maintained at a relatively constant level or set-point via negative feedback systems. We will try to determine the signal that informs the brain as to the actual level of adiposity at any given time and that therefore triggers appropriate weight-altering reflexes if needed. This research could potentially suggest novel approaches to the long-term therapy of obesity involving manipulation of this signal. A second method by which the CNS controls weight is through the size of individual meals. Several peptide hormones, including cholecystokinin (CCK) and somatostatin, have been reported to be endogenous satiety factors which limit meal size. The proposed research will look at the interactions of these hormones with other motivational variables known to affect meal size. Other proposed experiments will investigate the degree to which learning influences the neurally elicited metabolic events (such as the cephalic secretion of insulin) that occur when animals eat. Finally, one series of proposed experiments will study CNS glucoreceptive neurons; i.e., neurons are thought to be responsive to changes of blood glucose and to alter eating and hormone levels if they are too high or too low. Proposed experiments would investigate these cells through use of specific drugs to block their glucoreceptive action. These experiments should delineate for the first time the precise role of CNS glucoreceptors and their relationship to other glucoreceptors located throughout the body.